Sensitive CE-MS method for monitoring of riociguat and desmethylriociguat levels in human serum
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
260531/SVV/2020
Charles University project - International
GAUK 11920
Charles University project - International
GAUK - International
SVV - International
- Keywords
- Capillary electrophoresis, Desmethylriociguat, Determination, Mass spectrometry, Riociguat,
- MeSH
- Electrophoresis, Capillary methods MeSH
- Electrolytes MeSH
- Liquid-Liquid Extraction MeSH
- Spectrometry, Mass, Electrospray Ionization methods MeSH
- Humans MeSH
- Limit of Detection MeSH
- Linear Models MeSH
- Pyrazoles blood chemistry isolation & purification pharmacokinetics MeSH
- Pyrimidines blood chemistry isolation & purification pharmacokinetics MeSH
- Reproducibility of Results MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Electrolytes MeSH
- Pyrazoles MeSH
- Pyrimidines MeSH
- riociguat MeSH Browser
Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10-1000 ng/mL), with adequate accuracy (90.1-114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.
Department of Analytical Chemistry Faculty of Science Charles University Prague Czech Republic
Department of Hygiene 3rd Faculty of Medicine Charles University Prague Czech Republic
See more in PubMed
Kim, N. H., Delcroix, M., Jenkins, D.P., Channick, R., Dartevelle, P., Jansa, P., Lang I., Madani, M.M., Ogino, H., Pengo, V., Mayer E., J. Am. Coll. Cardiol. 2013, 62, D92-D99.
Toxvig, A. K., Wehland, M., Grimm, D., Infalnger, M., Krüger, M., Basic Clin. Pharmacol. Toxicol. 2019, 125, 202-214.
Frey, R., Becker, C., Saleh, S., Unger, S., van der Mey, D., Mück, W., Clin. Pharmacokinet. 2018, 57, 647-661.
Gnoth, M. J., Hopfe, P. M., Czembor, W., Bioanalysis 2015, 7, 193-205.
Michaličková, D., Jansa, P., Bursová, M., Hložek, T., Čabala, R., Hartinger, J. M., Ambrož, D., Aschermann, M., Lindner, J., Linhart, A., Slanař, O., Krekels, E. H. J., Pulm. Circ. 2020, 10, 1-11.
Štícha, M., Hložek, T., Bursová, M., Čabala, R., Jelínek, I., Electrophoresis 2019, 40, 2936-2945.
Peters, F. T., Drummer, O. H., Musshoff, F., Forensic Sci. Int. 2007, 165, 216-224.
